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Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.

Abstract : BACKGROUND & AIMS: Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. METHODS: In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM). RESULTS: Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration. CONCLUSIONS: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.
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Submitted on : Wednesday, May 27, 2009 - 7:16:53 PM
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Noël Cano, Jean-Marc Sturm, Alfred Meijer, Mohamad Yehia El-Mir, Robert Novaretti, et al.. Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.. Clinical Nutrition, Elsevier, 2004, 23 (3), pp.317-24. ⟨10.1016/j.clnu.2003.07.004⟩. ⟨inserm-00388990⟩



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